We plan research in two related areas to define, biochemically, mechanisms important in the pathogenesis of thrombotic disease in man. In studies using cultured human fibroblasts we hope to define the level of fatty acid synthesis in these cells and the carious mechanisms by which fatty acid synthesis is regulated in this tissue. We plan to study the effects of lipid both on the rates of synthesis of acetyl CoA carboxylase and on the short-term regulation of fatty acid synthesis in these cells. We will study the pathogenesis of the inherited hyperlipemias, obesity and diabetes using cultured fibroblasts from patients with these disorders. In studies of platelet physiology we hope to define the mechanism of the thrombin-induced platelet aggregation and release reaction using techniques of membrane biochemistry and structural analysis by electron microscopy. We plant to identify, characterize and isolate the cell surface receptor for thrombin on platelets; to elucidate the mechanism of the thrombin reaction both in regard to platelet structure and the relation of the thrombin reaction to the cAMP-protein kinase system.